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Analysis of the prion protein gene in multiple system atrophy

Neurodegenerative diseases are a very diverse group of disorders but they share some common mechanisms such as abnormally misfolded proteins with prion-like propagation and aggregation. Creutzfeldt-Jakob disease (CJD) is the most prevalent prion disease in humans. In the sporadic form of CJD the onl...

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Autores principales: Chelban, Viorica, Manole, Andreea, Pihlstrøm, Lasse, Schottlaender, Lucia, Efthymiou, Stephanie, OConnor, Emer, Meissner, Wassilios G., Holton, Janice L., Houlden, Henry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5156473/
https://www.ncbi.nlm.nih.gov/pubmed/27793473
http://dx.doi.org/10.1016/j.neurobiolaging.2016.09.021
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author Chelban, Viorica
Manole, Andreea
Pihlstrøm, Lasse
Schottlaender, Lucia
Efthymiou, Stephanie
OConnor, Emer
Meissner, Wassilios G.
Holton, Janice L.
Houlden, Henry
author_facet Chelban, Viorica
Manole, Andreea
Pihlstrøm, Lasse
Schottlaender, Lucia
Efthymiou, Stephanie
OConnor, Emer
Meissner, Wassilios G.
Holton, Janice L.
Houlden, Henry
author_sort Chelban, Viorica
collection PubMed
description Neurodegenerative diseases are a very diverse group of disorders but they share some common mechanisms such as abnormally misfolded proteins with prion-like propagation and aggregation. Creutzfeldt-Jakob disease (CJD) is the most prevalent prion disease in humans. In the sporadic form of CJD the only known risk factor is the codon 129 polymorphism. Recent reports suggested that α-synuclein in multiple system atrophy (MSA) has similar pathogenic mechanisms as the prion protein. Here we present 1 Italian family with MSA and prion disease. Also, cases of concurrent MSA and prion pathology in the same individual or family suggest the possibility of molecular interaction between prion protein and α-synuclein in the process of protein accumulation and neurodegeneration, warranting further investigations. We assessed the PRNP gene by whole-exome sequencing in 264 pathologically confirmed MSA cases and 462 healthy controls to determine whether the 2 diseases share similar risk factors. We then analyzed codon 129 polymorphism by Sanger sequencing and compared with previously published results in sporadic CJD. Homozygosity at codon 129 was present in 50% of pathologically confirmed MSA cases and in 58% of normal controls (odds ratio, 0.7 (95% confidence interval of 0.5–0.9)) compared with 88.2% in sporadic CJD. Our data show that the homozygous state of position 129 in the PRNP is not a risk factor for MSA. No other variants in the PRNP gene were associated with increased risk for MSA.
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spelling pubmed-51564732017-01-01 Analysis of the prion protein gene in multiple system atrophy Chelban, Viorica Manole, Andreea Pihlstrøm, Lasse Schottlaender, Lucia Efthymiou, Stephanie OConnor, Emer Meissner, Wassilios G. Holton, Janice L. Houlden, Henry Neurobiol Aging Genetic Report Abstract Neurodegenerative diseases are a very diverse group of disorders but they share some common mechanisms such as abnormally misfolded proteins with prion-like propagation and aggregation. Creutzfeldt-Jakob disease (CJD) is the most prevalent prion disease in humans. In the sporadic form of CJD the only known risk factor is the codon 129 polymorphism. Recent reports suggested that α-synuclein in multiple system atrophy (MSA) has similar pathogenic mechanisms as the prion protein. Here we present 1 Italian family with MSA and prion disease. Also, cases of concurrent MSA and prion pathology in the same individual or family suggest the possibility of molecular interaction between prion protein and α-synuclein in the process of protein accumulation and neurodegeneration, warranting further investigations. We assessed the PRNP gene by whole-exome sequencing in 264 pathologically confirmed MSA cases and 462 healthy controls to determine whether the 2 diseases share similar risk factors. We then analyzed codon 129 polymorphism by Sanger sequencing and compared with previously published results in sporadic CJD. Homozygosity at codon 129 was present in 50% of pathologically confirmed MSA cases and in 58% of normal controls (odds ratio, 0.7 (95% confidence interval of 0.5–0.9)) compared with 88.2% in sporadic CJD. Our data show that the homozygous state of position 129 in the PRNP is not a risk factor for MSA. No other variants in the PRNP gene were associated with increased risk for MSA. Elsevier 2017-01 /pmc/articles/PMC5156473/ /pubmed/27793473 http://dx.doi.org/10.1016/j.neurobiolaging.2016.09.021 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Genetic Report Abstract
Chelban, Viorica
Manole, Andreea
Pihlstrøm, Lasse
Schottlaender, Lucia
Efthymiou, Stephanie
OConnor, Emer
Meissner, Wassilios G.
Holton, Janice L.
Houlden, Henry
Analysis of the prion protein gene in multiple system atrophy
title Analysis of the prion protein gene in multiple system atrophy
title_full Analysis of the prion protein gene in multiple system atrophy
title_fullStr Analysis of the prion protein gene in multiple system atrophy
title_full_unstemmed Analysis of the prion protein gene in multiple system atrophy
title_short Analysis of the prion protein gene in multiple system atrophy
title_sort analysis of the prion protein gene in multiple system atrophy
topic Genetic Report Abstract
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5156473/
https://www.ncbi.nlm.nih.gov/pubmed/27793473
http://dx.doi.org/10.1016/j.neurobiolaging.2016.09.021
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